There are a number of known viscous or viscoelastic agents for ophthalmic surgical use (hereinafter “agents” or “viscoelastic agents”). For example, VISCOAT® (Alcon Laboratories, Inc.), which contains sodium hyaluronate and chondroitin sulfate; Provisc® (Alcon), Healon®, Healon® GV and Healon® 5 (Pharmacia & Upjohn), Amvisc® and Amvisc Plus® (Bausch & Lomb), and Vitrax® (Allergan), all of which contain essentially pure sodium hyaluronate (HA); and finally the hydroxypropylmethylcellulose (HPMC) products such as Cellugel® (Alcon). All of these highly purified products are useful in certain ocular surgical procedures, such as cataract surgery. They are used by the skilled ophthalmic surgeon for several surgical purposes, including maintenance of intraocular spaces, protection of ophthalmic tissues, particularly corneal endothelial cells, and as an aid in manipulating ophthalmic tissues. These agents are generally viscous enough to permit the skilled surgeon to use them for their intended surgical purposes, but not so viscous that expression of the agent through a cannula of acceptable bore size might be made difficult.
As suggested by the number of commercially available products, however, no one viscoelastic agent best fulfills all of the surgical purposes. Due to their particular physical characteristics, certain viscoelastic agents will be better suited for particular aspects of the surgical procedure. For example, in cataract surgery, the combination of relatively low molecular weight sodium hyaluronate and chondroitin sulfate found in the VISCOAT® product works well in maintaining the anterior chamber during capsulotomy, or anytime during the cataract procedure, and in adhering to and protecting tissues, particularly the corneal endothelium. However, due to its adhering and coating characteristics, the VISCOAT® product is more difficult to remove from the anterior chamber of the eye than some other agents. In addition, although it can be used to manipulate tissue for insertion of an intraocular lens (IOL) into the eye, certain other agents are better suited to perform this function.
Viscoelastic solutions of relatively high molecular weight sodium hyaluronate is having functionally desirable viscosity, such as Healon® or the PROVISO® product (Alcon Laboratories, Inc.) are highly cohesive, but relatively non-adherent with respect to the tissues they may contact during surgery. These characteristics make such solutions well suited for use as a soft tool for the gentle manipulation of delicate tissues during surgery. For example, these viscoelastic agents can be used to inflate the capsular bag and facilitate the insertion of an IOL. Their cohesiveness and lack of adhering quality also make them easier to remove from the eye at the end of surgery. However, sodium hyaluronate is not as effective as some agents in protecting ophthalmic tissues, especially during phacoemulsification procedures.
HPMC adheres well to ophthalmic tissues and therefore protects them, but does not perform as well as, for example, the VISCOAT® product, in maintaining the anterior chamber, or as well as sodium hyaluronate in manipulating tissues. However, it can be easily diluted with irrigation fluid for removal following IOL implantation. The removal of the viscous or viscoelastic agent at the close of surgery is generally effected to prevent or reduce the severity of intraocular pressure spikes following surgery.
In general, viscous solutions containing relatively higher molecular weight agents, including high molecular weight sodium hyaluronate, are more effective in maintaining the intraocular space than less viscous solutions containing relatively lower molecular weight agents; however, the high molecular weight agents tend to be highly cohesive and may be prematurely aspirated from a surgical site. This may occur, for instance, if they come into contact with the aspiration port of the phacoemulsification tip during a phacoemulsification procedure. The relatively lower molecular weight products, which due to their tenacious characteristics adhere to and protect tissues, are more difficult to remove from the surgical site.
In recognition of the fact that each of the foregoing agents has certain advantages and disadvantages for a given surgical procedure, the use of multiple viscoelastic agents in a single surgical procedure has been suggested. See, U.S. Pat. No. 5,273,056. The multiple viscoelastic approach has enjoyed some commercial success. Consider, for example, Pharmacia's Healon® series—each to product containing a different molecular weight fraction of sodium hyaluronate—or Alcon's DuoVisc® product, which contains both Provisc® and Viscoat®. The need remains, however, for a single viscoelastic agent that can adequately perform each of the functions associated with a given surgical procedure. The compositions of the present invention are believed to meet that need.
Commonly assigned U.S. patent application Ser. No. 09/857,543 discloses viscoelastic materials designed for use in otic surgery. Among the compositions disclosed therein is a formulation comprising 1.6% high molecular weight sodium hyaluronate and 4% chondroitin sulfate. The particular molecular weight ranges of the present invention, however, are neither disclosed nor suggested in that application, the contents of which are by this reference incorporated herein. Nor does that application suggest the unexpectedly improved performance realized by the present invention in ophthalmic surgery.
U.S. Pat. No. 6,051,560 discloses combinations of sodium hyaluronate and chondroitin sulfate for use in ophthalmic surgery. The commercial embodiment of that patent is found in the Viscoat® product, which, according to the package insert, contains 4% by weight chondroitin sulfate having a molecular weight of approximately 22,500 daltons and 3% by weight sodium hyaluronate having a molecular weight of over 500,000 daltons. As described above, the commercial product offers less than optimum performance in certain phases of the typical cataract surgical procedure. Quite unexpectedly, we have discovered that by modifying the molecular weight and concentrations of the polymeric components in the Viscoat® formulation, it is possible to create a viscoelastic agent that offers significantly improved overall performance compared to any of the products available on the market.